Metabolic plasticity as a strategy for virulence: participation of Candida albicans transcription factor RLM1 in host-pathogen interaction

Abstract

Candida albicans is an opportunistic fungus that is able to adapt to a wide range of host niches. The different carbon sources available in these niches support fungal growth and colonisation, but also promote profound rearrangements in cell wall architecture that affect immune detection and enhance C. albicans virulence. We have shown that C. albicans RLM1 participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources. In this study, we evaluated the effect of different carbon sources in response to cell wall damaging stress agents and in the interaction with macrophages. C. albicans Δrlm1/Δrlm1 mutant, wild-type and complemented strains were adapted to lactic acid or glucose, and the hypersensitivity of these cells to congo red, calcofluor white and caspofungin was assessed. Expression levels of genes involved in the cell adhesion and in the utilisation of alternative carbon sources were also evaluated by RT-PCR, using C. albicans cells adapted either to glucose or lactic acid. Additionally, we also studied the interaction of these cells with macrophages and the involvement of an essential cell wall component in this process. C. albicans cells adapted to different carbon sources, such as lactic acid, behave differently, affecting important virulence parameters, including stress resistance, adherence, biofilm formation, and infection outcome. This study supports the view that adaptive responses of Candida cells to alternative carbon sources present in host-niches increase the yeast fitness, impacting Candida-host interactions.